DNA polymerase of T4 plays a major role in spontaneous frameshift mutation. Using the T4 rII genetic system for measuring mutation, we have identified a number of polymerase mutant alleles which strongly increase frameshift mutation frequencies. The spectrum of frameshift production is unique to the polymerase mutation. To date, genetic positions of frameshift mutations have been determined and correlated to the wild type DNA sequence. The existence of the potential for the formation of DNA secondary structure in one frameshift region suggests a novel DNA structural precursor to frameshift mutation. Our studies indicate that the mechanisms of frameshift mutation are diverse and that the fidelity of DNA polymerases for base substitution mutation can be substantially different from frameshift mutation.